Physiology of Hair Growth. From early fetal development, and through the entire life of animals including humans, hair follicles (HFs) undergo many cycles of degeneration and regrowth. In human hair growth, during the neonatal period and throughout adolescence, HF on scalp progressively thicken because the follicles gradually enlarge with each new cycle (DeVillez R L: In: Current Concept, A Scope Publication, by the Upjohn Co., Kalamazoo, Mich., 1986; pp. 4-27; Takashima I, Kawagihi I: In: Toda K, et al (eds): Biology and Disease of Hair. Baltimore, Univ. Park Press, 1976; pp. 457-471).
The HP is composed of many cell types, such as epidermal and mesenchymal cells. The mesenchymal cells are known to play a role as "inductive organizers" of both fetal and postnatal follicles (Chase H B. Physiol Rev. 1954; 34:113-126).
The follicular germ cells, which are the bulbar matrix cells, are responsible for the great mitotic proliferation in the HF. During development, the cells in the matrix proliferate with an upward migration and differentiation into hair matrix, inner sheath and outer sheath cells. The hair matrix group, located in the central axis of the HF, further differentiates into the cells forming the medulla, hair cortex, and hair cuticle. These cells show a continuous upward migration with keratinization of the cortical and cuticle cells which are essential for the manufacturing process of hair in a growing follicle (Chase H B. Physiol Rev. 1954; 34:113-126; Hashimoto K. Br J Dermatol 1970; 83:167-176).
Hair cycles are divided into three stages: 1) Anagen, which is the active growing phase of the HF cycle, 2) Catagen, a regressive stage, 3) Telogen, resting stage. (DeVillez R L: In: Current Concept, a Scope Publication by the Upjohn Co., Kalamazoo, Mich., 1986; pp. 4-27.; Takashima I, Kawagishi I: In: Toda K, et al (eds): Biology and Desease of Hair. Baltimore, Univ. Park Press, 1976; pp. 457-471; Chase H B. Physiol Rev. 1954; 34:113-126; Kligman A M. J Invest Dermatol 1959; 33:307-316.) The relative duration of these stages varies with the individuals' age, hormonal factors, nutritional and health status, as well as genetics. Growth factors responsible for the stimulation of hair growth have not yet been elucidated.
Of the 100,000 to 150,000 scalp hairs on a human adult, approximately 90% are in anagen, with the remaining 10% in the telogen phase. Approximately 50 to 100 clubbed hairs are shed each day. The growth rates of human hairs vary slightly depending on the body region, with 0.44 mm/day at the vertex of the scalp then 0.27 mm/day for beard or body hair. (Moretti G, Rampini E, Rebora A: Int J Dermatol 15:277-285, 1976; Orentreich N, Durr N P: Clin Plast Surg 9:197-205, 1982; Katz M, Wheeler K E, Radowsky M. et al. Med biol Eng Comput 17:333-336, 1979.
In animal species such as rats and mice, all hairs are apparently in the same state of activity, where all cyclic changes are synchronized (DeVillez R L: In: Current Concept, A Scope Publication, by the Upjohn Co., Kalamazoo, Mich., 1986; pp. 4-27; Takashima I, Kawagihi I: In: Toda K, et al (eds): Biology and Disease of Hair. Baltimore, Univ. Park Press, 1976; pp. 457-471). The first cycle of hair growth in rats starts early after birth and continues through to approximately the 21st day of life. The second cycle starts approximately after day 35.
The young (8-12days) rat has been previously utilized as a model for chemotherapy-induced alopecia and a number of novel observations have been made (Hussein, A. M., Jimenez, J. J., McCall, C. A., and Yunis, A. A.: Science 249:1564, 1990; Jimenez, J. J., Wong, G. H. W., Yunis. A. A.: FASEB J. 5:2456, 1991; and Jimenez, J. J., Huang, H. S., and Yunis, A. A. Cancer Invest. 10(4):269, 1992; Jimenez, J. J. and Yunis, A. A.: Cancer Res. 52:413, 1992; Jimenez, J. J., Sawaya, M. E. and Yunis, A. A.: FASEB J. 6:911, 1992; Jimenez, J. J. and Yunis A. A.: Cancer Res. 52:5123, 1992; and Jimenez, J. J., Alvarez, E., Bustamante, C. D., and Yunis, A. A. Am. J. of the Med. Sci 310(2):43, 1995. Rats treated with chemotherapy during the first cycle of hair growth become totally alopecic within 10 days. These rats remain with total alopecia until the second cycle of hair growth. Thus it takes 20 to 30 days for rats to recover from the alopecia.
More recently, applicants have used a commercial hair remover, Neet.RTM., on rats during their first cycle of hair growth. This approach makes the rats immediately alopecic, and hair does not regrow until the second cycle. Applicants believe that this long latent period could be used effectively to test various substances for their potential ability to stimulate hair growth and thus shorten the time to recovery.
It is an object of the present invention to determine the possible existence of hair growth-stimulating activity or of hair growth-stimulating factors.